We have previously demonstrated that short-term cultures of nodular sclerosing Hodgkin's disease (NSHD) release a transforming growth factor into the serum-containing and serum-free media. This factor is not removed by removal of macrophages and is not secreted by the non-adherent lymphocytes or cloned fibroblasts. A short-term culture with partially purified Hodgkin's cells was a potent source of this factor. The activity in conditioned media is not interleukin-1 by bioassay measurement with mouse thymocytes. A transforming growth factor is present in the urine of patients with NSHD, and isolation and characterization is being performed. Acid/alcohol extraction of involved lymph nodes yields proteins which induce proliferation of fibroblasts in monolayer and colony formation by NRK cells when potentiated with 0.125 ng of EGF per 35-mm dish. The extracted material competes for the EGF receptor in fibroblast membranes with a significant down regulation of receptor number at 4 hours; however, the competition is less potent than that obtained with 1 ng of EGF per ml. In the coming year we will explore the production of fibroblast growth factor(s) by the L-428 Hodgkin's cell line and the HD#57 lymphoblastoid line. In addition, we will modify our extraction procedure to reduce the need for added EGF to obtain colony formation by NRK cells. Three breast cancer cell lines are being compared with these Hodgkin's cultures for the production of transforming growth factors.